Summary of Study ST001406

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000963. The data can be accessed directly via it's Project DOI: 10.21228/M86X2T This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Study ID	ST001406
Study Title	Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach (part-II)
Study Type	Subcutaneous adipose tissue (AT); Visceral AT; Liver Tissue; Plasma
Study Summary	Background: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for >80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.
Institute	Icahn School of Medicine at Mount Sinai
Department	Environmental Medicine and Public Health
Laboratory	High Resolution Exposomics Research Group
Last Name	Walker
First Name	Doug
Address	One Gustave L. Levy Place, Box 1057, New York, NY 10029
Email	douglas.walker@mssm.edu
Phone	212-241-9891
Submit Date	2020-06-19
Num Groups	4
Total Subjects	11
Num Males	1
Num Females	10
Study Comments	Upload #1: Visceral and subcutaneous abdominal adipose tissue, liver tissue. Plasma metabolomics are in upload #2
Publications	Valvi D, Walker DI, Inge T, Bartell SM, Jenkins T, Helmrath M, Ziegler TR, La Merrill MA, Eckel SP, Conti D, Liang Y, Jones DP, McConnell R, Chatzi L. (2020). Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach. Environment International. In Press.
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	GC-MS
Release Date	2021-06-19
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP001488
Sampleprep Summary:	Tissue POPs concentrations were measured in vAT, sAT and liver tissues collected during surgery. All tissue samples were prepared in batches of 11 study samples and 3 method blanks using a modified version of the QuECHERS method described by (Zamariola et al. 2017). Briefly, 0.2-0.5g of tissue was weighed, placed in an amber glass vial and treated with 3.5mL of LC-MS grade water. Each sample was then spiked with 50μL internal standard solution prepared in 2-proponal that was designed to represent environmental chemicals with a range of physiochemical properties to monitor analysis QA/QC, and included 500 ng/mL [13C6]-Anthracene, [13C12]-PCB28, [DIETHYL-D10]-Chlorpyrifos, [13C12]-PCB101, [13C12]-4,4'-DDE, [13C12]-PCB153, [13C12]-PCB180, [13C12]-PBDE47, [13C10]-Mirex, [13C6]-cis-Permethrin, [13C12]-PBDE99 and [13C12]-PBB153. Following addition of the internal standard solution, the sample was then homogenized for 1 min and placed in a sonicating bath for 10 min. The resulting homogenate was transferred to a 50 mL conical tube containing 10mL acetonitrile, 4000mg MgSO4 and1000mg NaCl, and vortexed for 5 min. After centrifuging, a 1.5mL aliquout was transferred to a cleanup tube containing 50 mg primary and secondary amine exchange material (PSA), 50 mg C18 and 150 mg MgSO4, vortex-mixed for 1 min and centrifuged at max speed for 5 min. From the supernatant, a 1 mL aliquot was transferred to a clean, glass tube and dried completely in a vacuum centrifuge operated at 35°C. The residue was then resuspended in 50μL isooctane and transferred to a GC vial containing a low volume insert and capped with a Teflon lined cap until analysis.
Sampleprep Protocol ID:	douglas_walker_Protocol_for_adipose_tissue_exposomics_v3_08Mar2018.pdf
Sampleprep Protocol Filename:	douglas_walker_Protocol_for_adipose_tissue_exposomics_v3_08Mar2018.pdf
Processing Storage Conditions:	Room temperature